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Neuroendocrine Interactions in the Control of Glucose- and Energy Homeostasis
Published in André Kleinridders, Physiological Consequences of Brain Insulin Action, 2023
The WNT pathway was first described in 1976 when it was reported that Drosophila Melanogaster has a wingless phenotype when this pathway is mutated (92). In 1982, the same signalling cascade was found to promote tumour formation in mice, and therefore given the term ‘integration-1 (int1)’ (93). ‘Wingless’ and ‘int1’ were later combined, and thus, the WNT pathway was coined. The WNT signalling pathway is evolutionarily highly conserved and is classically known for its role in embryogenesis and tumorigenesis (94). Its ligands (WNTs) are involved in three different pathways: the WNT/β-catenin pathway (also known as the canonical WNT pathway), the planar cell polarity pathway, and the WNT/Ca2+ pathway. The canonical WNT pathway is activated when a WNT ligand binds to the frizzled (Fzd) receptor, which subsequently forms a complex with the co-receptor lipoprotein related protein (LRP) 5/6. This causes dishevelled (Dvl) to phosphorylate LRP, which then inactivates GSK3β. Next, GSK3β inactivation decreases phosphorylation of the transcriptional co-activator β-catenin. Stabilized β-catenin then enters the nucleus where it associates with transcription factors of the lymphoid enhancer factor (LEF)/T cell factor (TCF) family, to ultimately regulate the transcription of downstream target genes such as cyclin D1 and axin 2 (95).
Bone Regeneration Effect of Cassia occidentalis Linn. Extract and Its Isolated Compounds
Published in Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay, Phytochemistry of Plants of Genus Cassia, 2021
Brijesh Kumar, Vikas Bajpai, Vikaskumar Gond, Subhashis Pal, Naibedya Chattopadhyay
In C3H10T1/2 cells, luteolin promotes osteogenic differentiation and in 3T3-L1 cells, it inhibits adipogenic differentiation. These effects are mediated by heat shock protein, Dnajb1 (DnaJ Hsp40) (Kwon et al., 2016). In human osteogenic sarcoma cell line, Saos2, luteolin, and its 8-C-glucopyranose analog orientin increased mineral content upon the induction of differentiation in the presence of β-glycerophosphate. At >10 μM, luteolin decreased the mineral content likely due to a pro-oxidant impact. At 50 μM, luteolin had a cytotoxic effect on osteoblasts as assessed by LDH release. Both luteolin and orientin inhibited the production of pro-inflammatory cytokines (TNFα and IL-6) from osteoblasts as well as sclerostin. Suppression of sclerostin by luteolin is likely to promote the osteogenic Wnt signaling (Nash et al., 2015). Furthermore, luteolin protected MC3T3-E1 cells against oxidative damage caused by H2O2 and menadione (Fatokun et al., 2015). From these reports, it appears that luteolin promotes osteoblast function and inhibits osteoclast function.
Microneedling
Published in Rubina Alves, Ramon Grimalt, Techniques in the Evaluation and Management of Hair Diseases, 2021
Rachita S. Dhurat, Sanober Burzin Daruwalla
Wnt signals play a key role in hair follicle morphogenesis, hair shaft differentiation and follicular cycling [18]. Activation of Wnt/β-catenin signaling is important not only for initiation and maintenance of hair morphogenesis but also for HF regeneration and growth of the hair shaft [19, 20]. Wnt3a and Wnt10b both mediate the canonical Wnt signaling pathway, which induces β-catenin stabilization [21]. In particular, Wnt10b prominently promoted proliferation and maintained trichogenesis-promoting ability [17].
Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice
Published in International Journal of Radiation Biology, 2023
Shashank Kumar, Eram Fathima, Farhath Khanum, Suttur S. Malini
The Wnt pathway contrarily has been shown to be an important role in early embryonic stem cell survival and maintenance (Wang and Wynshaw-Boris 2004) and in regulating hematopoietic stem cells in their niche environment (Rattis et al. 2004). Previous research has linked β-Catenin signaling to stem cell survival, tumorigenesis, and radiation. Clinically relevant doses of ionizing radiation enrich progenitors in murine mammary epithelial cell culture, and this enrichment is aided by β-Catenin stabilization (Rosen and Chen 2006. Studies with chronic myelogenous leukemia show that there are high levels of β-Catenin in small parental cell populations, leading to greater self-renewal capabilities and higher leukemia potential (Jamieson et al. 2004). Dysregulation of the Wnt/-Catenin signaling pathways in stem cell regulation has been proposed as one of the signaling pathways involved in carcinogenesis in the hematopoietic system (Reya and Clevers 2005). β-Catenin is required for both intercellular junctions and the canonical Wnt signaling pathway, which has been linked to cell survival (Choi et al. 2013). Recent research found that activating β-Catenin in granulocyte–macrophage progenitors in chronic myelogenous leukemia increased their self-renewal activity and leukemic potential (Jin et al. 2017). Furthermore, evidence has been shown in lung cancer, colorectal cancer, and gastrointestinal cancer for dysregulation of stem/progenitor cell self-renewal and maintenance via the Wnt/β pathway (Brabletz et al. 2005; He et al. 2005; Mishra et al. 2005; Reya and Clevers 2005; Chen et al. 2007; Lundin and Driscoll 2013).
Upregulation of miR-128 Mediates Heart Injury by Activating Wnt/β-catenin Signaling Pathway in Heart Failure Mice
Published in Organogenesis, 2021
Jing-Yao Li, Xin-Chang Li, Yu-Long Tang
Cascades of signaling pathways and a portfolio of genes have been identified to serve as potential targets for therapeutic interventions in the heart disorders.4–7 For example, cytosolic calcium homeostasis mediated by sarcoendoplasmic reticulum calcium ATPase (SERCA2a) is a critical regulator in respect to cardiac contraction.8,9 Wnt signaling is a well-known evolutionarily conserved and developmental signaling pathway for its role in various respects including inflammation, organ development, tissue homeostasis, embryogenesis, and injury repair.10,11 Over the past decade, the critical role of Wnt signaling has been recognized in cardiac physiology and pathophysiology. A canonical Wnt signaling pathway dominantly mediated by a central signal transducer β-catenin has been characterized to play notable roles in activation of heart regenerative process and heart remodeling in response to cardiac injury.12–14 Aberrant Wnt/β-catenin activation leads to onset and progression of cardiac dysfunction such as cardiac hypertrophy, fibrosis, arrhythmias, and infarction.15,16 Wnt1, a signature element of the early Wnt/β-catenin signaling, is a specific and potent inducer of angiogenesis and fibrosis in heart repair following acute cardiac injury.17 However, investigation and detailed understanding of molecular strategy of Wnt1/β-catenin pathway in pathophysiological cardiac hypertrophy and heart failure remain largely elusive.
Taking the road less traveled – the therapeutic potential of CBP/β-catenin antagonists
Published in Expert Opinion on Therapeutic Targets, 2021
The dichotomous roles of Wnt signaling in stem cell biology, in normal homeostasis and disease is a recurrent theme [21]. Most attempts to explain this dichotomy have relied either on the ‘antagonistic’ effects of ‘non-canonical’ versus ‘canonical’ Wnt signaling [21] or the ‘level’ of nuclear β-catenin driven transcription [9,22–24]. Antagonism” associated with the two Wnt pathways is an oversimplification. Non-canonical and canonical Wnt signaling coordinate to regulate cell fate determination and movement throughout various stages of developmental [25–27] and the small GTPases Rho, Rac and CDC42 directly link Wnt signaling to the cytoskeleton in both normal development (e.g. gastrulation) and in disease (e.g. metastasis) [26,28–32]. Additionally, the concept of the requirement for a ‘Goldilocks’ level for nuclear Wnt/TCF/β-catenin transcription does not explain the overall transcriptional response in pathogenesis versus normal homeostasis. For example, several studies have correlated increased Wnt/β-catenin signaling in colorectal tumors with worse prognosis [33–35], whereas in melanoma patients, active Wnt/β-catenin signaling, as judged by nuclear β-catenin in tumors, is associated with a more favorable prognosis [36–39].